Studies conducted during the past year: 1) have led to improved laboratory procedures for isolating and identifying isozyme variants of drug acetylating N-acetyltransferases, 2) have suggested that a genetic acetylation polymorphism similar to that in man and rabbit occurs in the non-human primate, baboon, 3) have shown that the mouse may be a suitable species for investigating the affect of genetic and environmental factors on the relative importance of enzymatic deacetylation and acetylation as influences on the elimination of amine-type drugs and foreign compounds from the body, 4) have been initiated using different human cell types which are accessible for pharmacogenetic study (e.g., RBC's, lymphocytes) as an avenue to study the regulation of drug acetylating enzymes in man, and to development of non-invasive methods to determine the human isoniazid acetylator phenotype, and 5) have initiated the development of a new method for screening dangerous amines, such as beta-naphthylamine, and benzidine, as potential substrates for the polymorphic isoniazid N-acetyltransferase. Investigation will be pursued in each of these areas during the coming year with the specific objectives of 1) assessing the possible role of the isoniazid acetylator polymorphism in the susceptibility of individuals to mutagenesis and carcinogenesis through studies in animals and animal tissues, and 2) of seeking correlations between the isoniazid acetylator phenotype and N-acetyltransferases located in various kinds of human cells such as the cellular componens of peripheral blood and skin. A broader objective of this work is to further our understanding of the human pharmacology and pharmacogenetics of drugs and foreign substances which are metabolized by acetylation. BIBLIOGRAPHIC REFERENCES: W.W. Weber and S.N. Cohen. Aging effects and drugs in man. Handbook of Experimental Pharmacology. Eds. J.R. Gillette and J.R. Mitchell. Springer-Verlag, Heidelberg, New York, Vol. 28, pt. 3, Chap. 66, pp. 213-230, 1975. W.W. Weber, J.N. Miceli, D.J. Hearse, and G.S. Drummond. N-acetylation of drugs. Pharmacogenetic studies in rabbits selected for their acetylator characteristics. Drug Metab. and Disp. 4(1), 1976.